This project explores the relationship between minor physical anomalies (MPAs) and Attention-deficit Hyperactivity Disorder (ADHD). These minor dysmorphic features may be of major diagnostic significance, indicating general classes of altered morphogenesis or specific malformation syndromes. Our primary goal has been to apply quantitative and clinical MPA diagnostic methods to a population of ADHD boys. We have examined combinations of individual MPAs chosen to reflect embryological factors. Since brain and craniofacial morphology arise from common primordia and are molded by shared forces, it is hypothesized that a pathological process results in both psychopathology and dysmorphology. Thus, specific classes of dysmorphology may delineate brain maldevelopment in ADHD. In the first stage of this project, we have found specific embryologically-determined classes of MPAs in ADHD, reflecting specific developmental mechanisms: (a) the chronological origin of dysmorphogenesis, (b) type of alteration (malformation versus deformation), and (c) specific embryonic primordia ("Anlagen") giving rise to MPAs. In our next stage of research, we propose to extend these findings to address the following questions: (1) Do dysmorphic phenotypes differ for ADHD patients as a function of response to stimulant medication? Pilot studies suggest that both favorable and non-favorable responders are dysmorphic, but in different, biologically interpretable ways. (2) Are the patterns and extent of ADHD dysmorphology found in boys also present in girls? Preliminary data suggest that they too are dysmorphic. (3) Are craniofacial MPAs and brain dysmorphology correlated in ADHD, as predicted by their embryological relationship? We will determine whether brain morphology is abnormal in ADHD patients (a) in general, or (b) as a function of medication response, and (c) whether patterns of brain and craniofacial dysmorphology cohere within subjects in (a) and (b).